Synthesis of novel fenfuram-diarylether hybrids as potent succinate dehydrogenase inhibitors

Twelve novel fenfuram-diarylether hybrids were designed, synthesized and characterized by ¹H NMR and MS. Their in vitro antifungal activities were evaluated against five phytopathogenic fungi by mycelial growth inhibition method. Most compounds showed significant antifungal effect on Rhizoctonia solani and Sclerotinia sclerotiorum. Compound 1c exhibited the most potent antifungal effect on R. solani with an EC₅₀ value of 0.242 mg/L, superior to the commercial fungicide boscalid (EC₅₀ = 1.758 mg/L) and the lead fungicide fenfuram (EC₅₀ = 7.691 mg/L). Molecular docking revealed that compound 1c featured a higher affinity for succinate dehydrogenase (SDH) than fenfuram. Furthermore, it was shown that the 2-chlorophenyl group of compound 1c formed a π-π stacking with D/Tyr-128 and a Cl-π interaction with B/His-249, which made compound 1c more active than fenfuram against SDH.     

Design,synthesis and antifungal activity of novel fenfuram-diarylamine hybrids

Ten novel fenfuram-diarylamine hybrids were designed and synthesized. And their antifungal activities against four phytopathogenic fungi have been evaluated in vitro and most of the compounds demonstrated a significant antifungal activities against Rhizoctonia solani and Sclerotinia sclerotiorum. Compound 5e exhibited the most potent antifungal activity against R. solani with an EC₅₀ value of 0.037 mg/L, far superior to the commercially available fungicide boscalid (EC₅₀ = 1.71 mg/L) and lead fungicide fenfuram (EC₅₀ = 6.18 mg/L). Furthermore, scanning electron microscopy images showed that the mycelia on treated media grew abnormally with tenuous, wizened and overlapping colonies compared to the negative control. Molecular docking studies revealed that compound 5e featured a higher affinity for succinate dehydrogenase (SDH) than fenfuram. Furthermore, it was shown that the 3-chlorophenyl group in compound 5e formed a CH-π interaction with B/Trp-206 and a Cl-π interaction with D/Tyr-128, rendering compound 5e more active than fenfuram against SDH.     

Phenolic composition and medicinal usage of Psidium guajava Linn.: Antifungal activity or inhibition of virulence?

Psidium guajava is a Myrtaceae plant whose medicinal properties are recognized in several locations. The use of teas and tinctures prepared from their leaves has been used to combat infections caused by fungi of the genus Candida. In this study, aqueous extracts of leaves and hydroethanolic were tested to verify the antifungal potential and its chemical composition has been investigated. The microbiological assays were performed by broth microdilution to determine the minimum inhibitory concentration (MIC) and from these the minimum fungicidal concentration was performed (MFC) by subculturing on solid media. A cell viability curve was obtained for demonstration of inhibition of fungal growth of strains of Candida albicans and Candida tropicalis. Tests to check morphological changes by the action of the extracts were performed in microcultive cameras depleted environment at concentrations of MIC/2, MIC and MIC × 2. Extracts analyzed by high performance liquid chromatography demonstrated flavonoids and phenolic acids. The extracts showed fungistatic effect and no fungicide with MIC >8192 μg/mL, MFC above 8192 μg/mL. The IC₅₀ was calculated ranging from 1803.02 to 5623.41 μg/mL. It has been found that the extracts affect the morphological transition capability, preventing the formation of pseudohyphae and hyphae. Teas and tinctures, therefore, have the potential antifungal, by direct contact, causing inhibition of fungal multiplication and its virulence factor, the cell dimorphism, preventing tissue invasion. Further studies are needed to elucidate the biochemical pathways and genes assets involved in these processes.     

Synergysm of voriconazole or itraconazole with other antifungal agents against species of Fusarium

BackgroundInfections caused by Fusarium are difficult to treat because these fungi show in vitro and in vivo resistance to practically all the antifungal agents available, which explains the high mortality rates. An attempt to overcome fungal resistance is the combination of antifungal agents, especially those with different mechanisms of action.AimsEvaluate the in vitro interactions of combinations of voriconazole or itraconazole with other antifungal agents against 32 isolates of Fusarium spp.: Fusarium chlamydosporum, Fusarium oxysporum, Fusarium proliferatum and Fusarium solani.MethodsDrug interactions were assessed by a checkerboard microdilution method that also included the determination of the MIC of each drug alone according to CLSI (Clinical and Laboratory Standards Institute) document M38-A2, 2008.ResultsThe best combinations were voriconazole + terbinafine which showed synergism against 84% of Fusarium strains. Other synergistic combinations were voriconazole + itraconazole (50%), voriconazole + fluconazole (50%), voriconazole + miconazole (38%), voriconazole + flucytosine (22%) and voriconazole + ketoconazole (25%). The synergisms observed with itraconazole combinations were itraconazole + terbinafine (25%) and itraconazole + flucytosine (9.37%). The antagonisms observed were: voriconazole + fluconazole (3%) and itraconazole + flucytosine (12.5%).ConclusionsThe synergism showed by voriconazole + terbinafine was remarkable. To better elucidate the potential usefulness of our findings, new in vivo and in vitro studies deserve be performed.     

Biological and molecular responses of Chironomus riparius (Diptera,Chironomidae) to herbicide 2,4-D (2,4-dichlorophenoxyacetic acid)

2,4-Dichlorophenoxyacetic acid (2,4-D) is an agricultural contaminant found in rural ground water. It remains to be determined whether neither 2,4-D poses environmental risks, nor is the mechanism of toxicity known at the molecular level. To evaluate the potential ecological risk of 2,4-D, we assessed the biological parameters including the survival rate, adult sex ratio of emerged adults, and mouthpart deformities in Chironomus riparius after long-term exposure to 2,4-D. The larvae were treated with 0.1, 1 or, 10 μg L^? 1 of 2,4-D for short- and long-term exposure periods. The sex ratio was changed in C. riparius exposed to only 10 μg L^? 1 of 2,4-D, whereas mouthpart deformities were observed as significantly higher in C. riparius exposed to 0.1 μg L^? 1 of 2,4-D. Survival rates were not significantly affected by 2,4-D. Furthermore, we evaluated the molecular and biochemical responses of biomarker genes such as gene expression of heat shock proteins (HSPs), ferritins and glutathione S-transferases (GSTs) in C. riparius exposed to 2,4-D for 24 h. The expressions of HSP70, HSP40, HSP90 and GST levels in C. riparius were significantly increased after exposure to a 10 μg L^? 1 concentration of 2,4-D, whereas ferritin heavy and light chain gene expressions were significantly increased at all concentrations of 2,4-D exposure. Finally, these results may provide an important contribution to our understanding of the toxicology of 2,4-D herbicide in C. riparius. Moreover, the 2,4-D-mediated gene expressions may be generated by 2,4-D is the causative effects on most probable cause of the observed alterations. These biological, molecular and morphological parameters and the measured parameters can be used to monitor 2,4-D toxicity in an aquatic environment.     

Actividad antifúngica de los enjuagues bucales frente a Candida albicans y Rhodotorula mucilaginosa: un estudio in vitro

BackgroundCandida albicans and Rhodotorula mucilaginosa are yeasts of clinical importance in the oral cavity. In immunocompromised patients they can cause some pathologies that must be controlled with antimicrobials.AimsTo evaluate and compare the antimicrobial efficacy of commercially available mouthrinses against strains of C. albicans and R. mucilaginosa.MethodsThe six mouthwashes studied in vitro were formulated (alone or in combination) with chlorhexidine (CHX) 0.12%, CHX 0.1%, CHX 0.05%, cetylpyridinium chloride (CPC) 0.075%, CPC 0.05%, and essential oils. Ten C. albicans and R. mucilaginosa isolates each were studied. The agar diffusion method (Mueller Hinton II), with incubation at 32 °C was used to evaluate the antifungal activity.ResultsThe results of this study indicate that mouthwashes with CHX 0.1%, CHX 0.12%, CHX 0.05% + CPC 0.05%, CHX 0.12% + CPC 0.05% and CPC 0.075% have an antifungal effect against C. albicans and R. mucilaginosa. CHX 0.1% led to the broadest inhibition zone for C. albicans and R. mucilaginosa (25.65 ± 2.39 mm and 40.05 ± 3.31 mm). Essential oils did not show any antifungal activity. Statistical analysis showed no statistical difference between mouth rinses CHX 0.1%, CHX 0.12% and CHX 0.12% + CPC 0.05% (p = 0.0001) against C. albicans and R. mucilaginosa.ConclusionsMouthwashes with CHX showed higher antifungal activity against C. albicans and R. mucilaginosa than other mouthwashes studied.     

Actividad antifúngica in vitro de la micafungina

BackgroundMicafungin is a new and very useful pharmacological tool for the treatment of invasive mycoses with a wide antifungal spectrum for the most common pathogenic fungi. Micafungin is especially active against the genera Candida and Aspergillus. Its antifungal mechanism is based on the inhibition of the β-1,3- D-glucan synthesis, an essential molecule for the cell wall architecture, with different con sequences for Candida and Aspergillus, being micafungin fungicide for the former and fungistatic for the latter.AimTo describe the in vitro antifungal spectrum of micafungin based in the scientific and medical lite rature of recent years.MethodsWe have done a bibliographic retrieval using the scientific terms, “micafungin”, “activity”, “Candida”, “Aspergillus”, “fungi”, “mycos*”, “susceptibility”, in PubMed/Medline from the National Library of Medicine de EE.UU. from 2005 to 2009.ResultsWe can underline that most than 99% of Candida isolates are susceptible to ≤ 2 μg/ml of micafungin. MIC are very low (≤ 0.125 μg/ml) for most clinical isolates of the species Candida albicans, Candida glabrata, Candida tropicalis and Candida krusei while Candida parapsilosis and Candida guilliermondii isolates are susceptible to anidulafungin concentrations ≤ 2 μg/ml. The activity of micafungin is excellent against those medical important species of Aspergillus. However, its activity is very low against Cryptococcus and the Zygomycetes.ConclusionsThe excellent activity of micafungin has made this antifungal a first line therapeutic indication for candidemia and invasive candidiasis in non-neutropenic patients.     

Synergistic antifungal activity of statin–azole associations as witnessed by Saccharomyces cerevisiae- and Candida utilis-bioassays and ergosterol quantification

BackgroundFrequent opportunist fungal infections and the resistance to available antifungal drugs promoted the development of new alternatives for treatment, like antifungal drug combinations.AimsThis work aimed to detect the antifungal synergism between statins and azoles by means of an agar-well diffusion bioassay with Saccharomyces cerevisiae ATCC 32051 and Candida utilis Pr_1–2 as test strains.MethodsSynergistic antifungal effects were tested by simultaneously adding a sub inhibitory concentration (SIC) of statin (atorvastatin, lovastatin, pravastatin, rosuvastatin or simvastatin) plus a minimal inhibitory concentration (MIC) of azole (clotrimazole, fluconazole, itraconazole, ketoconazole or miconazole) to yeast-embedded YNB agar plates, and a positive result corresponded to a yeast growth inhibition halo higher than that produced by the MIC of the azole alone. Yeast cell ergosterol quantification by RP-HPLC was used to confirm statin–azole synergism, and ergosterol rescue bioassays were performed for evaluating statin-induced ergosterol synthesis blockage.ResultsGrowth inhibition was significantly increased when clotrimazole, fluconazole, itraconazole, ketoconazole and miconazole were combined with atorvastatin, lovastatin, rosuvastatin and simvastatin. Highest growth inhibition increments were observed on S. cerevisiae (77.5%) and C. utilis (43.2%) with a SIC of simvastatin plus a MIC of miconazole, i.e. 4 + 2.4 μg/ml or 20 + 4.8 μg/ml, respectively. Pravastatin showed almost no significant effects (0–7.6% inhibition increase). Highest interaction ratios between antifungal agents corresponded to simvastatin–miconazole combinations and were indicative of synergism. Synergism was also confirmed by the increased reduction in cellular ergosterol levels (S. cerevisiae, 40% and C. utilis, 22%). Statin-induced ergosterol synthesis blockage was corroborated by means of ergosterol rescue bioassays, pravastatin being the most easily abolished inhibition whilst rosuvastatin being the most ergosterol-refractory.ConclusionsSelected statin–azole combinations might be viable alternatives for the therapeutic management of mycosis at lower administration doses or with a higher efficiency.     

Evaluating agro-industrial by-products as dietary roughage source on growth performance of fattening steers

Silages from pineapple peel, sweet corn husk and cob mixed with bagasse and vinasse were evaluated to determine their chemical composition and fermentation characteristics as well as feeding performance in fattening steers. The experiment, which lasted 90 days, involved 48 fattening steers (264 ± 37.4 kg BW) randomly allocated to three diets. Treatments included: a control diet containing rice straw and molasses (T1); diet containing bagasse–vinasse mixture including sweet corn husk and cob silage (BS; T2); and diet containing bagasse–vinasse mixture including pineapple peel silage (BP; T3). All treatments included a commercial concentrate feed (13% CP) and ad libitum rice straw throughout the experiment. Results from chemical analysis showed that dry matter (DM) of BS was higher than BP (P < 0.05), whereas the protein content of BS and BP was similar (P > 0.05). For fermentation characteristics, pH in BP was lower than BS (P < 0.05); in addition, acetic and butyric acids in BS were higher than BP (P < 0.05). Findings from growth trial showed that total DM intake in steers fed T1 was higher compared to the other dietary treatments (P < 0.05), whereas the average BW gain was found to be grater in T3 steers (P < 0.05). As result from our findings, bagasse–vinasse mixture with pineapple peel silage appeared to be a viable feed ingredient in fattening steer diet and moreover it could become an economically feasible agro-industrial by-product for farmers.     

Isolation and identification of antifungal peptides from Bacillus BH072, a novel bacterium isolated from honey

A bacterial strain BH072 isolated from a honey sample showed antifungal activity against mold. Based on morphological, biochemical, physiological tests, and analysis of 16S rDNA sequence, the strain was identified to be a new subspecies of Bacillus sp. It had a broad spectrum of antifungal activity against various mold, such as Aspergillus niger, Pythium, and Botrytis cinerea. Six pairs of antifungal genes primers were designed and synthesized, and ituA, hag, tasA genes were detected by PCR analysis. The remarkable antifungal activity could be associated with the co-production of these three peptides. One of them was purified by 30–40% ammonium sulfate precipitation, Sephadex G-75 gel filtration and anion exchange chromatography on D201 resin. The purified peptide was estimated to be 35.615 kDa and identified to be flagellin by micrOTOF-Q II. By using methanol extraction, another substance was isolated from fermentation liquor, and determined to be iturin with liquid chromatography–mass spectrometry (LC–MS) method. The third possible peptide encoded by tasA was not isolated in this study. The culture liquor displayed antifungal activity in a wide pH range (5.0–9.0) and at 40–100 °C. The result of the present work suggested that Bacillus BH072 might be a bio-control bacterium of research value.     

Synthesis and biological evaluation of novel trichodermin derivatives as antifungal agents

To discover more potential antifungal agents, 17 novel trichodermin derivatives were designed and synthesized by modification of 3 and 4a. The structures of all the synthesized compounds were confirmed by ¹H NMR, ESI-MS and HRMS. Their antifungal activities against Ustilaginoidea oryzae and Pyricularia oryzae were evaluated. Most of the target compounds showed potent inhibitory activity, in which 4g showed superior inhibitory effects than 4a and commercial fungicide prochloraz. Furthermore, 4h demonstrated comparable inhibitory activity to 4a. Moreover, 4i and 4l exhibited excellent inhibitory activity for Pyricularia oryzae. Additionally, compound 9 was found to be more active against all tested fungal strains than 3, with EC₅₀ values of 0.47 and 3.71 mg L⁻¹, respectively.     

Characterization of Paecilomycescinnamomeus from the camellia whitefly, Aleurocanthus camelliae (Hemiptera: Aleyrodidae), infesting tea in Japan

The whitefly, Aleurocanthus camelliae Kanmiya and Kasai (Hemiptera: Aleyrodidae), is an invasive species in Japan that was first discovered in 2004 on tea in Kyoto. Soon after its arrival epizootics of an entomopathogenic fungus were observed in populations of the whitefly in many tea-growing regions. Here we identify this fungus as Paecilomyces cinnamomeus (Petch) Samson and W. Gams (Hypocreales: Clavicipitaceae) based on morphological characteristics and molecular analyses. This is the first record of P. cinnamomeus in Japan and also the first time it has been recorded from the genus Aleurocanthus. A isolate of P. cinnamomeus caused greater than 50% and 90% infection in whitefly nymphs at 1 × 10⁶ and 1 × 10⁷ conidia/ml respectively, while the commercial mycoinsecticides Preferd® (Isaria fumosorosea) and Mycotal® (Lecanicillium muscarium) caused <10% infection at their recommended field rates (5 × 10⁶ and 9 × 10⁶ conidia/ml, respectively), suggesting that P. cinnamomeus may be more useful as a control agent than the currently available mycoinsecticides. Optimum and upper limit temperatures for in vitro growth of P. cinnamomeus isolates were 22.5–25 °C and 32.5 °C, respectively. At field rates, the fungicide thiophanate-methyl caused some inhibition of in vitro growth of P. cinnamomeus isolates, and the bactericide copper oxychloride and the insecticides tolfenpyrad and methidathion were strongly inhibitory. The findings obtained in this study will be useful in the development of microbial control programs using P. cinnamomeus against A. camelliae.     

Additive and synergistic effects of Bacillus spp. isolates and essential oils on the control of phytopathogenic and saprophytic fungi from medicinal plants and marigold seeds

Contamination of plants and seeds with microorganisms is one of the main problems in the production and distribution of various agricultural products, as well as raw herbal material for the preparation of herbal remedies. In targeting microbial contamination, among other bacteria, Bacillus species showed a significant capacity for biocontrol. The antifungal activity of 14 isolates of Bacillus spp. against 15 fungal isolates from medicinal plants was examined utilizing a dual plate assay. The strongest and broadest antagonistic activity against all fungi tested was exhibited by isolates SS-12.6 and SS-13.1 (from a 43% to 74% reduction in fungal growth), while isolates SS-39.1 and SS-39.3 were effective against the fewest fungus species and also had the weakest antifungal activity. The effect of a crude lipopeptide extract (CLE) of Bacillus sp. SS-12.6 was similar to that achieved by a dual culture with isolate SS-12.6, confirming that the antagonism was the result of the antifungal activities of lipopeptides. In addition, essential oils of thyme (0.55 mg/mL) and savory (0.32 mg/mL) in various combinations with the CLE of SS-12.6 were tested for antifungal activity, and additive and synergistic effects for some of the fungi were obtained. When testing the effect of CLE, oils (0.40 mg/mL for thyme oil and 0.21 mg/mL for savory oil) and combinations in situ on marigold seeds, a reduction of total fungal infection without an adverse effect on germination was accomplished by 6-h treatments with CLE of SS-12.6 (85% reduction of fungal infection and 63% germination), supernatant from liquid culture of SS-12.6 (more than 90% reduction of fungal infection with 69% seed germination) and combinations of CLE and savory oil (77% reduction of fungal infection and 62% seed germination) and CLE with thyme and savory oils (about 75% reduction of fungal infection with 69% seed germination).     

Cytotoxic,antimicrobial activities,AChE and BChE inhibitory effects of compounds from Tanacetum chiliophyllum (Fisch. & Mey.) Schultz Bip. var. oligocephalum (D.C.) Sosn. and T. chiliophyllum (Fisch. & Mey.) Schultz Bip. var. monocephalum Grierson

Tanacetum L. species traditionally used for insecticidal purposes as well as in folk medicine for their antitumor, antimicrobial, antifungal activities. In our previous study a novel sesquiterpene lactone and triterpene lactone together with 12 known flavonoids, coumarin and a triterpene were isolated from T. chiliophyllum var. oligocephalum and T. chiliophyllum var. monocephalum extracts which have insecticidal and antimicrobial activity. In this study, cytotoxic, antimicrobial activities and acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory effects of pure compounds isolated from these plants were investigated. The tested compounds showed AChE and BChE inhibition which ranged between 7.20–80.37% and 9.19%–76.99% respectively. The highest AChE and BChE inhibition was observed for ulubelenolide which afforded 80.37% and 76.99% inhibition respectively. The cytotoxic effect of the compounds ranged between 22.34–49.77 μg/mL IC₅₀ values. Highest cytotoxic activity was observed against MCF-7 and HEK 293 cell line by 5–hydroxy-3′,4′,7-trimethoxy flavone and 5-hydroxy-3′,4′,6,7-tetramethoxyflavone that produced 25.80 ± 0.17 and 22.34 ± 0.70 IC₅₀ values respectively. Compounds eupatilin, cirsilineol, 5–hydroxy-3′,4′,7-trimethoxy flavone and ulubelenolide showed significant antimicrobial effect on C. albicans with 7.8 μg/mL MIC. The new compound ulubelenolide afforded high AChE and BChE inhibition as well as high antifungal activity. In our opinion activity of this substance should be evaluated further against other fungal species.     

In vitro micropropagation of Dracaena sanderiana Sander ex Mast: An important indoor ornamental plant

A protocol has been developed for in vitro plant regeneration from a nodal explant of Dracaena sanderiana Sander ex Mast. Nodal explant showed high callus induction potentiality on MS medium supplemented with 6.78 μM 2,4-dichlorophenoxyacetic acid (2,4-D) followed by 46.5 μM chlorophenoxy acetic acid (CPA). The highest frequency of shoot regeneration (85%) and number of shoots per explant (5.6) were obtained on medium supplemented with 7.84 μM N⁶-benzylaminopurine (BA). Rooting was high on MS solid compared to liquid medium when added with 7.38 μM indole-3-butyric acid (IBA). Fifty percent of the roots were also directly rooted as microcuttings on soil rite, sand and peat mixture (1:1:1). In vitro and ex vitro raised plantlets were used for acclimatization. More than 90% of the plantlets was successfully acclimatized and established in plastic pots. Ex vitro transferred plantlets were normal without any phenotypic aberrations.     

Antibiofilm activity and post antifungal effect of lemongrass oil on clinical Candida dubliniensis isolate

Candidal infections are often difficult to eradicate due to the resistance of biofilms to antifungal agents. This study aimed at determining the effects of lemongrass (Cymbopogon citratus DC) oil against Candida dubliniensis in both planktonic and biofilms form. The results from broth microdilution method revealed that the minimum inhibitory and minimum fungicidal concentration of lemongrass oil on C. dubliniensis were 0.43 and 0.86 mg/ml, respectively. Employing a formazan salt (XTT tetrazolium) reduction assay for biofilm study, the results showed that the average percentage (mean ± SD) inhibition of lemongrass oil (0.43 mg/ml) on biofilm formation was 91.57 ± 1.31%, while it exhibited more than 80% killing activity against C. dubliniensis in biofilm at concentrations of 1.7 mg/ml. In addition, a significant reduction (P = 0.03) of candidal adhesion to acrylic occurred after a 15 min exposure to 1.7 mg/ml of lemongrass oil. Moreover, limited exposure of yeasts to lemongrass oil at subcidal concentration can suppress growth for more than 24 h. Altogether, the results obtained indicate that lemongrass oil possessed antifungal and antibiofilm activities and could modulate candidal colonization. Therefore, the efficacy of lemongrass oil merits further development of this agent for the therapy of oral candidiasis.     

Antifungal peptides homologous to the Penicillium chrysogenum antifungal protein (PAF) are widespread among Fusaria

Putative antifungal peptide encoding genes containing Penicillium chrysogenum antifungal protein (PAF) characteristic amino acid motifs were identified in 15 Fusarium isolates, representing 10 species. Based on the predicted sequences of mature peptides, discrepancy in one, two or three amino acids was observed between them. Phylogenetic investigations revealed that they show high amino acid sequence similarity to PAF and they belong to the group of fungal derived antifungal peptides with PAF-cluster. Ten from the 15 partially purified <10 kDa peptide fraction of Fusarium ferment broths showed antifungal activity. The presence of approximately 6.3 kDa molecular weight peptides was detected in all of the antifungally active ferment broths, and this peptide was isolated and purified from Fusarium polyphilaidicum. The minimal inhibitiory concentrations of F. polyphilaidicum antifungal protein (FPAP) were determined against different filamentous fungi, yeasts and bacteria. Filamentous fungal species were the most susceptible to FPAF, but some yeasts were also slightly sensitive.     

Effective control of black Sigatoka disease using a microbial fungicide based on Bacillus subtilis EA-CB0015 culture

Black Sigatoka disease caused by the fungus Mycosphaerella fijiensis Morelet is the most devastating disease of bananas worldwide. Its management is reliant on protectant and systemic fungicides despite their environmental concerns. This study evaluated the effect of a microbial fungicide (MF) based on Bacillus subtilis EA-CB0015 and its metabolites for the control of black Sigatoka disease on banana plants in greenhouse and field conditions. The MF applied at 1.5 L/ha and 3.0 L/ha provided control of the disease comparable to the protectant fungicide chlorothalonil in greenhouse. In the field, the MF applied in solution with water at 0.15 L/ha and 1.5 L/ha every 11 days during 10 weeks reduced black Sigatoka disease severity in 20.2% and 28.1% respectively; reductions comparable to those obtained with the protectant fungicides chlorothalonil (1.5 L/ha) and mancozeb (3.8 L/ha). The MF incorporated into different programs with systemic fungicides reduced disease level up to 42.9% with no significant differences with the conventional program. To determine which component of the MF is responsible for the activity against M. fijiensis, greenhouse and in vitro tests were set up to evaluate individually the spores, vegetative cells and secondary metabolites of B. subtilis EA-CB0015. All components reduced the severity of the disease and the germination of ascospores. For both trials the activity of the metabolites was higher and comparable to the activity obtained with the MF, indicating that the efficacy of the MF depends mainly on the metabolites and in lesser extent to B. subtilis EA-CB0015 cells.     

Monte Carlo study of the influence of energy spectra,mesh size,high Z element on dose and PVDR based on 1-D and 3-D heterogeneous mouse head phantom for Microbeam Radiation Therapy

PurposeTo evaluate the influence of energy spectra, mesh sizes, high Z element on dose and PVDR in Microbeam Radiation Therapy (MRT) based on 1-D analogy-mouse-head-model (1-D MHM) and 3-D voxel-mouse-head-phantom (3-D VMHP) by Monte Carlo simulation.MethodsA Microbeam-Array-Source-Model was implemented into EGSnrc/DOSXYZnrc. The microbeam size is assumed to be 25 μm, 50 μm or 75 μm in thickness and fixed 1 mm in height with 200 μm c-t-c. The influence of the energy spectra of ID17@ESRF and BMIT@CLS were investigated. The mesh size was optimized. PVDR in 1-D MHM and 3-D VMHP was compared with the homogeneous water phantom. The arc influence of 3-D VMHP filled with water (3-D VMHWP) was compared with the rectangle phantom.ResultsPVDR of the lower BMIT@CLS spectrum is 2.4 times that of ID17@ESRF for lower valley dose. The optimized mesh is 5 µm for 25 µm, and 10 µm for 50 µm and 75 µm microbeams with 200 µm c-t-c. A 500 μm skull layer could make PVDR difference up to 62.5% for 1-D MHM. However this influence is limited (<5%) for the farther homogeneous media (e.g. 600 µm). The peak dose uniformity of 3-D VMHP at the same depth could be up to 8% for 1.85 mm × 1 mm irradiation field, whereas that of 3-D VMHWP is <1%. The high Z element makes the dose uniformity enhance in target. The surface arc could affect the superficial PVDR (from 44% to 21% in 0.2 mm depth), whereas this influence is limited for the more depth (<1%).ConclusionAn accurate MRT dose calculation algorithm should include the influence of 3-D heterogeneous media.